In recent years, percutaneous absorption adhesive preparations for external use such as various types of cataplasmas and tapes have been developed using ointment bases and pressure-sensitive adhesives, as percutaneous absorption preparations for use in the administration of drugs into the living body through the skin.
As the method for effectively releasing drugs from these adhesion type percutaneous absorption preparations and efficiently effecting their absorption by the living body from the skin, various methods have been proposed in which, for example, concentration of the drug to be contained is increased or a percutaneous penetration enhancer is jointly used. These methods improve percutaneous absorption of drugs, but the pressure-sensitive adhesive property of the percutaneous absorption preparation is frequently reduced to cause a so-called stringiness and adhesive residue on the skin surface.
As means for resolving these problems, various methods have been proposed, such as a method in which fine powder silica is added to a pressure-sensitive adhesive (JP-A-2-295565; the term "JP-A" as used herein means an "unexamined published Japanese patent application") or a method in which pressure-sensitive characteristics are controlled by making an ointment base into gel form through crosslinking of a pressure-sensitive adhesive (JP-A-3-220120).
Of these methods, the method in which fine powder silica is added to a pressure-sensitive adhesive is used in various field, because it is generally known that fine powder silica acts as a rheology agent to change flow characteristics of pressure-sensitive adhesives.
However, the method in which fine powder silica is added cannot improve pressure-sensitive adhesive characteristics in some cases depending on the formulation composition and formulation method of pressure-sensitive adhesives. Particularly, decrease in the viscosity of pressure-sensitive adhesives cannot be prevented when a polar substance such as polyethylene glycol is added in a large amount as a percutaneous penetration enhancer.
On the other hand, the method in which entire portion of a pressure-sensitive adhesive is crosslinked by external crosslinking to make it into gel form is markedly excellent in view of the point that the pressure-sensitive adhesive characteristics can be controlled even when a percutaneous penetration enhancer and other additives are used in a large amount.
This method, however, also cannot be used in the case where the percutaneous absorption preparation contains a substance having a crosslinking inhibition action, because the pressure-sensitive adhesive cannot fully be crosslinked. In particular, when a generally and frequently used multifunctional isocyanate is used as a crosslinking agent, addition of a drug or additive having a hydroxyl group, an amino group, a carboxyl group or a mercapto group to the pressure-sensitive adhesive causes crosslinking inhibition. For the reason, the drugs and additives having these functional groups cannot be used.
In addition, techniques in which a percutaneous absorption preparation is produced by making a pressure-sensitive adhesive into granular form are disclosed for example in JP-B-58-12255 (the term "JP-B" as used herein means an "examined Japanese patent publication") and JP-B-58-23367, but these techniques have a difficulty in obtaining appropriate pressure-sensitive adhesive characteristics in the case where a percutaneous penetration enhancer and other additives are used in a large amount.